Management of flu-like syndrome with cetirizine in patients with relapsing-remitting multiple sclerosis during therapy with interferon beta: Results of a randomized, cross-over, placebo-controlled pilot study

Doriana Landi, Maria Albanese, Fabio Buttari, Fabrizia Monteleone, Laura Boffa, Silvia Rossi, Caterina Motta, Elisa Puma, Diego Centonze

Research output: Contribution to journalArticle

Abstract

Background: Flu-like syndrome (FLS) is a common adverse event experienced by patients with relapsing-remitting multiple sclerosis (RRMS) treated with interferon beta (IFNβ). FLS can lead to poor treatment adherence and early IFNβ discontinuation. The involvement of interleukin-6 (IL-6) in the occurrence of FLS has been suggested. We hypothesized that cetirizine, a second-generation histamine H1 receptor antagonist able to reduce the levels of IL-6, might improve IFNβ-induced FLS. Methods: We conducted a pilot, cross-over, randomized, placebo-controlled, double-blind study to evaluate the efficacy of cetirizine 10 mg added after each IFNβ injection to the standard of care for FLS (acetaminophen or nonsteroidal anti-inflammatory drugs) on FLS in patients with RRMS treated with IFNβ. Patients were randomized to two treatment sequences: 1) 4-week treatment with placebo added to the standard treatment for FLS, followed by 4-week treatment with cetirizine added to the standard of care, and 2) first addition of cetirizine, then of placebo. The primary efficacy endpoint was the mean change of FLS severity [11-point visual analog scale (VAS)] after 4 weeks of treatment within each sequence. Results: Forty-five patients (71.1% female, mean age 39.1 years, mean time from RRMS diagnosis 5.8 years) were randomized to treatment sequences 1 and 2. The differences between cetirizine and placebo in the intensity of FLS were not statistically significant: total mean VAS scores at 4 hours from IFNβ injection were 3.57 and 3.42 for cetirizine and placebo, respectively (difference –0.15; 95% confidence interval: from –0.74 to 0.44; p = 0.6029). The two treatments were similar also with regard to other efficacy measures considered and to the safety/tolerability profile. Conclusions: The addition of cetirizine to the standard of care for IFNβ-induced FLS in patients with RRMS does not seem to provide significant benefits compared with placebo. Further effort is required to understand the mechanisms underlying IFNβ-induced FLS. Trial registration: EudraCT 2013-001055-12.

Original languageEnglish
Article numbere0165415
JournalPLoS One
Volume12
Issue number7
DOIs
Publication statusPublished - Jul 1 2017

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Cetirizine
interferon-beta
Relapsing-Remitting Multiple Sclerosis
Interferon-beta
sclerosis
influenza
placebos
Placebos
therapeutics
Standard of Care
Therapeutics
Interleukin-6
Visual Analog Scale
interleukin-6
Histamine H1 Antagonists
Acetaminophen
injection
acetaminophen
Injections
nonsteroidal anti-inflammatory agents

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Management of flu-like syndrome with cetirizine in patients with relapsing-remitting multiple sclerosis during therapy with interferon beta : Results of a randomized, cross-over, placebo-controlled pilot study. / Landi, Doriana; Albanese, Maria; Buttari, Fabio; Monteleone, Fabrizia; Boffa, Laura; Rossi, Silvia; Motta, Caterina; Puma, Elisa; Centonze, Diego.

In: PLoS One, Vol. 12, No. 7, e0165415, 01.07.2017.

Research output: Contribution to journalArticle

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abstract = "Background: Flu-like syndrome (FLS) is a common adverse event experienced by patients with relapsing-remitting multiple sclerosis (RRMS) treated with interferon beta (IFNβ). FLS can lead to poor treatment adherence and early IFNβ discontinuation. The involvement of interleukin-6 (IL-6) in the occurrence of FLS has been suggested. We hypothesized that cetirizine, a second-generation histamine H1 receptor antagonist able to reduce the levels of IL-6, might improve IFNβ-induced FLS. Methods: We conducted a pilot, cross-over, randomized, placebo-controlled, double-blind study to evaluate the efficacy of cetirizine 10 mg added after each IFNβ injection to the standard of care for FLS (acetaminophen or nonsteroidal anti-inflammatory drugs) on FLS in patients with RRMS treated with IFNβ. Patients were randomized to two treatment sequences: 1) 4-week treatment with placebo added to the standard treatment for FLS, followed by 4-week treatment with cetirizine added to the standard of care, and 2) first addition of cetirizine, then of placebo. The primary efficacy endpoint was the mean change of FLS severity [11-point visual analog scale (VAS)] after 4 weeks of treatment within each sequence. Results: Forty-five patients (71.1{\%} female, mean age 39.1 years, mean time from RRMS diagnosis 5.8 years) were randomized to treatment sequences 1 and 2. The differences between cetirizine and placebo in the intensity of FLS were not statistically significant: total mean VAS scores at 4 hours from IFNβ injection were 3.57 and 3.42 for cetirizine and placebo, respectively (difference –0.15; 95{\%} confidence interval: from –0.74 to 0.44; p = 0.6029). The two treatments were similar also with regard to other efficacy measures considered and to the safety/tolerability profile. Conclusions: The addition of cetirizine to the standard of care for IFNβ-induced FLS in patients with RRMS does not seem to provide significant benefits compared with placebo. Further effort is required to understand the mechanisms underlying IFNβ-induced FLS. Trial registration: EudraCT 2013-001055-12.",
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T2 - Results of a randomized, cross-over, placebo-controlled pilot study

AU - Landi, Doriana

AU - Albanese, Maria

AU - Buttari, Fabio

AU - Monteleone, Fabrizia

AU - Boffa, Laura

AU - Rossi, Silvia

AU - Motta, Caterina

AU - Puma, Elisa

AU - Centonze, Diego

PY - 2017/7/1

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N2 - Background: Flu-like syndrome (FLS) is a common adverse event experienced by patients with relapsing-remitting multiple sclerosis (RRMS) treated with interferon beta (IFNβ). FLS can lead to poor treatment adherence and early IFNβ discontinuation. The involvement of interleukin-6 (IL-6) in the occurrence of FLS has been suggested. We hypothesized that cetirizine, a second-generation histamine H1 receptor antagonist able to reduce the levels of IL-6, might improve IFNβ-induced FLS. Methods: We conducted a pilot, cross-over, randomized, placebo-controlled, double-blind study to evaluate the efficacy of cetirizine 10 mg added after each IFNβ injection to the standard of care for FLS (acetaminophen or nonsteroidal anti-inflammatory drugs) on FLS in patients with RRMS treated with IFNβ. Patients were randomized to two treatment sequences: 1) 4-week treatment with placebo added to the standard treatment for FLS, followed by 4-week treatment with cetirizine added to the standard of care, and 2) first addition of cetirizine, then of placebo. The primary efficacy endpoint was the mean change of FLS severity [11-point visual analog scale (VAS)] after 4 weeks of treatment within each sequence. Results: Forty-five patients (71.1% female, mean age 39.1 years, mean time from RRMS diagnosis 5.8 years) were randomized to treatment sequences 1 and 2. The differences between cetirizine and placebo in the intensity of FLS were not statistically significant: total mean VAS scores at 4 hours from IFNβ injection were 3.57 and 3.42 for cetirizine and placebo, respectively (difference –0.15; 95% confidence interval: from –0.74 to 0.44; p = 0.6029). The two treatments were similar also with regard to other efficacy measures considered and to the safety/tolerability profile. Conclusions: The addition of cetirizine to the standard of care for IFNβ-induced FLS in patients with RRMS does not seem to provide significant benefits compared with placebo. Further effort is required to understand the mechanisms underlying IFNβ-induced FLS. Trial registration: EudraCT 2013-001055-12.

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